The synthetic nucleoside beta-L-2′-deoxythymidine (L-dT) is known in the art. Antonin Holy first disclosed beta-L-2′-deoxythymidine and methods for preparing beta-L-2′-deoxythymidine in 1972 in “Nucleic Acid Components and Their Analogs. CLIII. Preparation of 2′-deoxy-L-Ribonucleosides of the Pyrimidine Series,” Collect. Czech. Chem. Commun. (1972), 37(12), 4072–87. The compound is represented by the following chemical structure:
wherein R is H.
Several authors have reported antiviral activity of beta-L-2′-deoxythymidine against herpes simplex virus. See, e.g., Iotti et al., WO 92/08727; and Spadari et al., J. Med. Chem. (1992), 35(22), 4214–20.
More recently, Gilles Gosselin, Jean-Louis Imbach and Martin Bryant disclosed that the compound and its derivatives and analogues have useful properties against the hepatitis B virus. See WO 00/09531; PCT US01/17301 and PCT US01/19147; U.S. Pat. Nos. 6,395,716; 6,569,837; 6,444,652; and 6,566,344. L-dT is currently in advanced clinical development by Idenix Pharmaceuticals, Inc. (Cambridge, Mass.).
Each of the foregoing references discloses a synthetic process for producing L-dT that relies upon crystallizing the compound from ethanol. None of the references disclose the particular crystalline or physical form of the L-dT that was obtained, or the water content of such L-dT. However, it has been recognized that crystalline, amorphous, hydrated, and various physical forms of the same compound can vary substantially in their biological properties, and in their ease of processing, manufacturing and/or pharmaceutical formulation. In addition, some forms are unstable under ambient conditions and thus require special storage and handling conditions to be maintained, or must be avoided altogether.
Given the commercial importance of beta-L-2′-deoxythymidine, it would be useful to have additional forms and phases of beta-L-2′-deoxythymidine that may exhibit beneficial properties in manufacturing or other applications. It is therefore an objective of this invention to provide novel forms and phases of beta-L-2 ′-deoxythymidine.
It is another objective to provide novel methods for the preparation and isolation of forms and phases of beta-L-2′-deoxythymidine.
It is still another objective of the invention to provide therapeutic uses of such forms and phases of beta-L-2′-deoxythymidine.